Dear Dr. West,
I do really appreciate to have such a forum to support and inform cancer patients of the latest treatments and challenges in the field. I myself have been struggling with lung cancer for the past 2 years (already tired), but have been supported and uplifted by my family and colleagues at works (thank god for them).
I need support in my apparent cancer recurrence: 1.2 yrs on Tarceva w/o progression (no previous chemo), CEA and CA-125 starts again to increase, PET scan done this month shows 0.6 cm in one lymph node and pericardial fluid (i.e. Stage IV), I am a liver transplant (done in 2001), and with fluctuating creatinine levels.
I am wondering on the efficacy of the following treatment options, and what is been said as the best course for progress free survival:
1. Afatinib
2. Gefitinib
3. Erlotinib + Pemetrexed
4. Erlotinib + Cisplatin
5. Erlotinib + Radiation
6. Avastin
I appreciate if you could provide some insight into these options, as I am now at this crossroad and very anxious on how to move forward.
Thanks GRACE for such a big help....
Reply # - October 27, 2014, 06:38 AM
Hi hj1947,
Hi hj1947,
Welcome to GRACE. I think the first issue to consider is whether your cancer actually is progressing, and if it is progressing to such an extent that you need to change your treatment. In the setting of previously established metastatic lung cancer, swollen lymph nodes and the appearance of an effusion are always suspicious for cancer, but each of these conditions can have causes other than cancer, and the lymph node size is not excessive. In addition, rising CEA and CA-125 values are not always a reliable indicator of progression - the only two definitive ways to determine the existence of progression are scan results and clinical symptoms. Of course, if creatinine levels are a problem, a dose reduction or treatment change might be necessary.
The doctors here have often expressed the opinion that a patient should not rush to switch from a targeted therapy which has been effective for a significant period of time (as yours has). Dr. West uses the analogy of "bad brakes vs. no brakes" - if the targeted therapy continues to keep progression at a slow rate, that may be a better result than the unknown effect of a different drug. Furthermore, although new drugs are always being tested and approved, there are a limited number of them available, and you want to get the maximum benefit from each one you use.
As far as the specific regimens you list, though it has been approved as a first-line treatment for patients with activating EGFR mutations, afatinib has not shown good results after another EGFR TKI such as Tarceva has stopped working. And since gefitinib is very similar to Tarceva, there isn't any evidence that it can help when taken after Tarceva.
The results of the recent IMPRESS trial have cast a great deal of doubt over the idea of combining Tarceva with a chemo agent. You can read about that trial here.
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Reply # - October 27, 2014, 06:46 AM
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At times, focal radiation is considered if there is just one area of cancer which is progressing while the rest is well-controlled. Normally in the setting of metastatic lung cancer, a local treatment such as surgery or radiation is only favored when there are symptoms such as pain to relieve. You can read the GRACE FAQ on this subject here. The possibility of using radiation is something you would need to discuss with your oncologist and a radiation oncologist.
Finally, the use of Avastin as a single agent following progression on Tarceva is not generally considered an option.
If after consulting with your doctor it is determined that you need to change treatment, other choices would be standard chemo agents such as Taxotere (doctaxel) or if your cancer is non-squamous Alimta (pemetrexed), or a clinical trial of a new agent which focuses on acquired resistance to Tarceva (if you have an activating EGFR mutation).
Good luck with your treatment choice, if one is deemed necessary.
JimC
Forum moderator
Reply # - October 27, 2014, 07:57 AM
Jim has already done a great
Jim has already done a great job laying the groundwork here. Indeed, just as Jim says, I'd question whether there is enough evidence of progression to do anything. I am actually increasingly against checking CEAs or other serum tumor markers, as well as doing PETscans: both of these approaches seem to all too frequently lead to vague hints of progression that are simply not significant. We don't like to discard effective therapies too early. Discarding a well tolerated treatment based on just a rise in CEA and an equivocal finding or two on PET is a sharme.
In terms of other options once true progression is documented, it's very reasonable to radiate a solitary growing lesion or perhaps two. I have no enthusiasm for Gilotrif (afatinib) or Iressa (gefitinib) after progression on Tarceva (erlotinib) -- there is very little evidence that they work to any meningful degree. There is a provocative trial with afatinib and Erbitux (cetuximab), an anti-EGFR antibody, that looks encouraging but needs to be tested further before it could be considered a strong option. Similarly, while there is some evidence that the combination of Avastin (bevacizumab) with Tarceva prolongs the time before disease progression in EGFR mutation-positive NSCLC, and it's how I now prefer to treat patients just diagnosed with EGFR mutation-positive advanced NSCLC, it's not clear that adding Avastin to Tarceva after progression on Tarceva alone is helpful. I've done it occasionally in the past and have achieved as much as 6-8 months of disease stability after seeing prior progression on Tarceva alone, but that's not a common approach and hasn't been tested in studies.
As Jim noted, our enthusiasm for continuing Tarceva or another oral EGFR inhibitor while adding chemo to it is much lower now after the results of the IMPRESS trial demonstrated that this provided no improvement in progression-free survival and may be detrimental in terms of overall survival.
Good luck.
-Dr. West